Anisotropic biocomposite material, medical implants comprising same and methods of treatment thereof

ABSTRACT

Reinforced biocomposite materials. According to at least some embodiments, medical implants are provided that incorporate novel structures, alignments, orientations and forms comprised of such reinforced bioabsorbable materials, as well as methods of treatment thereof.

FIELD OF THE INVENTION

The present invention is of anisotropic biocomposite material, medicalimplants comprising same and methods of treatment thereof, and inparticular to such material, implants and methods of treatment that havemedical applications.

BACKGROUND OF THE INVENTION

The mechanical strength and modulus (approximately 3-5 GPa) ofnon-reinforced resorbable polymers is insufficient to support fracturedcortical bone, which has an elastic modulus in the range ofapproximately 15-20 GPa. For example, in an article the bending modulusof human tibial bone was measured to be about 17.5 GPa (Snyder S MSchneider E, Journal of Orthopedic Research, Vol. 9, 1991, pp. 422-431).Therefore, the indications of existing medical implants constructed fromresorbable polymers are limited and their fixation usually requiresprotection from motion or significant loading. These devices arecurrently only a consideration when fixation of low stress areas isneeded (i.e. non-load bearing applications) such as in pediatricpatients or in medial malleolar fractures, syndesmotic fixation,maxillofacial, or osteochondral fractures in adults.

A new class of reinforced composite biomaterials (biocomposites) hasbeen recently introduced wherein a bioabsorbable and biocompatiblepolymer is reinforced by bioabsorbable, biocompatible glass fibers.These materials can achieve improved mechanical properties. Thesematerials also involve a compatibilizer to bind the polymer to thereinforcing fibers. Examples of such materials are described in thefollowing two patent applications, which are included fully herein byreference as if fully set forth herein:

1. Biocompatible composite and its use (WO2010122098)

2. Resorbable and biocompatible fibre glass compositions and their uses(WO2010122019)

These materials have been further described and characterized inpublications associated with these patents including

-   1. Lehtonen T J et al. Acta Biomaterialia 9 (2013) 4868-4877-   2. Lehtonen T J et al. J Mech Behavior BioMed Materials. 20 (2013)    376-386

The development of this class of materials described in the backgroundart has focused on the composition of the materials: the bioabsorbablepolymer, the reinforcing mineral fiber, the compatibilizer, and thecombinations between them.

These compositions have been demonstrated to be capable of achievingmechanical properties superior to the mechanical properties previouslyachieved with bioabsorbable polymers alone.

However, while material composition is one parameter that can affectmechanical properties of a medical implant, when it comes to compositematerials, the material composition does not by itself ensure mechanicalproperties that are sufficient for the implant to achieve its desiredbiomechanical function. In fact, reinforced composite medical implantswith identical compositions and identical geometries can have vastlydifferent mechanical properties. Furthermore, even within the sameimplant, mechanical properties can vary greatly between differentmechanical axes and between different types of mechanical strengthmeasurements.

SUMMARY OF THE INVENTION

The background art does not teach or suggest biocomposite materials thathave one or more desirable mechanical characteristics. The backgroundare also does not teach or suggest such materials that can achieve adesired biomechanical function.

By “biocomposite material” it is meant a composite material that isbiologically compatible or suitable, and/or which can be brought intocontact with biological tissues and/or which can be implanted intobiological materials and/or which will degrade, resorb or absorbfollowing such implantation.

By “biocompatible” it is meant a material that is biologicallycompatible or suitable, and/or which can be brought into contact withbiological tissues, and/or which can be implanted into biologicalmaterials.

The present invention, in at least some embodiments, relates toreinforced biocomposite materials which overcome the drawbacks of thebackground art. According to at least some embodiments, medical implantsare provided that incorporate novel structures, alignments, orientationsand forms comprised of such reinforced bioabsorbable materials. Thesemedical implants have unique mechanical properties. They have greatclinical benefit in that these implants can have mechanical propertiesthat are significant greater than those of the currently availablebioabsorbable polymer implants. The term “mechanical properties” asdescribed herein may optionally include one or more of elastic modulus,tensile modulus, compression modulus, shear modulus, bending moment,moment of inertia, bending strength, torsion strength, shear strength,impact strength, compressive strength and/or tensile strength.

According to at least some embodiments, the implants have improvedmechanical properties in at least one mechanical axis or parameter ascompared with at least one other mechanical axis or parameter within thesame implant. The implants can therefore be considered anisotropic. Amechanical axis as defined herein can be any line drawn through theimplant, optionally passing through the center of the implant. Amechanical parameter as defined herein can include bending strength andstiffness (resistance to bending force), tensile strength and stiffness(resistance to tensile force), compression strength and stiffness(resistance to compression force), shearing strength and stiffness(resistance to shearing force), or torsional strength and stiffness(resistance to torsional force).

Optionally, the improved mechanical properties in one axis or parameterare increased by at least 50% as compared with another axis or parameterand are preferably increased by at least 100%, more preferably by atleast 200%, 300%, 400%, and most preferably by at least 500% or anyintegral value in between.

Optionally, the improved mechanical properties in one axis or parameterof the implant are alternatively or additionally increased by at least50% as compared with an implant of identical composition but withamorphous or non-aligned internal structure and are preferably increasedby at least 100%, more preferably by at least 200%, 300%, 400%, and mostpreferably by at least 500% or any integral value in between.

Optionally, the improved mechanical property is strength and thestrength in one axis or parameter is increased by at least 50 MPa ascompared with another axis or parameter. Preferably, the strength isincreased by at least 100 MPa, more preferably by at least 200 MPa, 300MPa, 400 MPa, and most preferably by at least 500 MPa or any integralvalue in between.

Optionally, the improved mechanical property is strength and thestrength in one axis or parameter of the implant is alternatively oradditionally increased by at least 50 MPa as compared with an implant ofidentical composition but with amorphous or non-aligned internalstructure, and preferably are increased by at least 100 MPa, morepreferably by at least 200 MPa, 300 MPa, 400 MPa, and most preferably byat least 500 MPa or any integral value in between.

Optionally, the improved mechanical property is elastic modulus and themodulus in one axis or parameter is increased by at least 3 GPa ascompared with another axis or parameter. Preferably, the modulus isincreased by at least 5 GPa, more preferably by at least 8 GPa, 12 GPa,16 GPa, and most preferably by at least 20 GPa or any integral value inbetween.

Optionally, the improved mechanical property is elastic modulus and themodulus in one axis or parameter of the implant is alternatively oradditionally increased by at least 3 GPa as compared with an implant ofidentical composition but with amorphous or non-aligned internalstructure. Preferably, the modulus is increased by at least 5 GPa, morepreferably by at least 8 GPa, 12 GPa, 16 GPa, and most preferably by atleast 20 GPa or any integral value in between.

According to at least some embodiments, anisotropocity of one or moresegments of implant in one mechanical axis as compared with amorphous(non-aligned) material is preferably greater than 10%, 50%, 100%, 200%,300%, 500% or any integral value in between.

According to at least some embodiments, anisotropocity of one or moresegments of implant in one mechanical axis as compared with another axisis preferably greater than 10%, 50%, 100%, 200%, 500%, 1000% or anyintegral value in between.

According to at least some embodiments, there is provided relativehigher strength in one mechanical axis as compared with another (e.g.bending over tensile) of 10%, 50%, 100%, 200%, 300% or any integralvalue in between.

According to at least some embodiments, there is provided relativehigher elastic modulus as measured in one mechanical axis as comparedwith another of 10%, 30%, 50%, 100%, 200% or any integral value inbetween.

Without wishing to be limited by a closed list or a single hypothesis,the biocomposite implants described herein represent a significantbenefit over metal or other permanent implants (including non absorbablepolymer and reinforced polymer or composite implants) in that they areabsorbable by the body of the subject receiving same, and thus theimplant is expected to degrade in the body following implantation. Againwithout wishing to be limited by a closed list or a single hypothesis,they also represent a significant benefit over prior absorbable implantssince they are stronger and stiffer than non-reinforced absorbablepolymer implants in at least one mechanical axis. In fact, thesereinforced composite polymer materials can even approach the strengthand stiffness of cortical bone, making them the first absorbablematerials for use in load bearing orthopedic implant applications.

On an underlying level, there is a great difference between thereinforced biocomposite implants and previous implants from metal,plastic, and other traditional medical implant materials. Traditionalmedical implant materials are isotropic such that their mechanicalproperties are identical in all axes. This simplifies implant design asthe mechanical strength of the implant is determined solely based on thegeometry of the implant and the inherent material properties of thematerial. Without wishing to be limited by a closed list or a singlehypothesis, for reinforced biocomposite implants, the inherent materialproperties of the biocomposite (i.e. the biocomposite in amorphous ornon-aligned form) are actually quite low and can approximate themechanical properties of the polymer alone. As such, implant geometriesfor implants constructed from these biocomposite materials does notinherently determine implants that are mechanically strong or stiff.

However, the medical implants of the present invention in at least someembodiments are able to exceed the mechanical properties of previousbioabsorbable implants, including previous biocomposite implants in oneor more mechanical axes and in one or more mechanical parameters.Preferably these implants feature structures and forms in which thereinforcing fibers are aligned within the implant in order to providethe implant load bearing strength and stiffness in the axes in whichthese properties are biomechanically required. Thus, either the entireimplant or segments of the implant are anisotropic (i.e. they havedifferent mechanical properties in different axes). With theseanisotropic implants, the implant mechanical design cannot rely solelyon the geometry of each part. Rather, the specific alignment of thereinforcing fibers within the implant and the resulting anisotropicmechanical profile are a key parameter in determining the biomechanicalfunction of the implant.

Aside from the mechanical considerations related to the anisotropicmedical implants, there are additional limitations in that medicalimplants using these reinforced biocomposite materials cannot bedesigned according to existing implant designs due to the limitationsassociated with producing parts from these composite materials.

For example, metal implants or permanent polymer implants may beproduced by machining. Even fiber-reinforced permanent polymer implantsmay be machined without adversely affecting the mechanical properties.However, absorbable, reinforced composite material implants cannot bemachined without causing damage to the underlying material sincemachining will expose reinforcing fibers from the polymer, thus causingtheir strength to degrade quickly once they are directly exposed to bodyfluid following implantation.

At the other end of the spectrum, pure polymer or very short (<4 mm)fiber-reinforced polymer implants may be manufactured usingstraightforward injection molding processes. Injection molding of thesematerials does not, however, result in sufficiently strong implants.Therefore, specialized designs and production methods are required inorder to design and produce an implant that can benefit from thesuperior mechanical properties of the previously described reinforcedbioabsorbable composite materials.

The term “biodegradable” as used herein also refers to materials thatare degradable, resorbable or absorbable in the body.

The term “load bearing” optionally also includes partially load bearing.According to various embodiments, the load bearing nature of the device(implant) may optionally include flexural strengths above 200 MPa,preferably above 300 MPa, more preferably above 400 MPa, 500 MPa, andmost preferably above 600 MPa or any integral value in between.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. The materials, methods, andexamples provided herein are illustrative only and not intended to belimiting.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin order to provide what is believed to be the most useful and readilyunderstood description of the principles and conceptual aspects of theinvention. In this regard, no attempt is made to show structural detailsof the invention in more detail than is necessary for a fundamentalunderstanding of the invention, the description taken with the drawingsmaking apparent to those skilled in the art how the several forms of theinvention may be embodied in practice.

In the drawings:

FIG. 1 shows some exemplary plates according to at least someembodiments of the present invention;

FIG. 2 shows the anisotropic properties of a bio-composite plate asdemonstrated by the large difference in mechanical properties of sampleswith identical compositions, but with a majority of layers aligned ateither 0° (Parallel) or 90° (Perpendicular) to the longitudinal axis ofthe implant sample (n=4);

FIGS. 3A and 3B show representative examples of samples. FIG. 3A shows asample with majority of layers with fiber orientation perpendicular toimplant longitudinal axis. FIG. 3B shows a sample with majority oflayers with fiber orientation parallel to implant longitudinal axis;

FIG. 4 shows that the anisotropic properties of a bio-composite plateare directly affected by fiber orientation, as demonstrated by the largedifference in mechanical properties of samples with identicalcompositions, but with non-aligned layers (Amorphous) or with layersaligned at either 0° (Parallel) or 90° (Perpendicular) to thelongitudinal axis of the implant sample (n=4);

FIG. 5A-C show representative sample examples. FIG. 5A shows anamorphous fiber orientation sample; FIG. 5B shows a sample with majorityof layers with fiber orientation perpendicular to implant longitudinalaxis. FIG. 5C shows a sample with majority of layers with fiberorientation parallel to implant longitudinal axis;

FIG. 6 shows elastic modulus after exposure of exemplary biocompositesamples to forced degradation;

FIG. 7 shows flexural strength after exposure of exemplary biocompositesamples to forced degradation;

FIGS. 8A and 8B are photographs of a representative hollow pin implant,5 cm length, 2 mm OD, 1 mm ID. FIG. 8A is a photo of the pin along itslength; FIG. 8B is a photo of the cross-section of the pin;

FIGS. 9A and 9B are photographs of a representative pin, 5 cm length, 2mm OD. FIG. 9A is a photo of the pin along its length; FIG. 9B is aphoto of the cross-section of the pin.

FIG. 10 shows the decrease in mechanical properties due to incubationunder conditions that force degradation; and

FIGS. 11A and 11B demonsrate a graphical finite elements simulation.FIG. 11A shows force distribution on a hollow cylinder pin implant witha wall thickness made of 5 layers as demonstrated in FIG. 11B.

DETAILED DESCRIPTION OF SOME EMBODIMENTS

A medical implant according to at least some embodiments of the presentinvention is suitable for load-bearing orthopedic implant applicationsand comprises one or more bioabsorbable materials where sustainedmechanical strength and stiffness are critical for proper implantfunction.

According to at least some embodiments of the present invention, thereis provided orthopedic implants, such as those for bone fixation, madefrom reinforced bioabsorbable composite materials. Specifically,implants according to at least some embodiments incorporatecharacteristics, features, or properties that can either only beachieved using the reinforced bioabsorbable composite materials or arespecifically advantageous for implants comprised of these types ofmaterials, or optionally a combination of both in a single implant.

Without wishing to be limited by a closed list, the material-specificdesign benefits are optionally provided by one or more of the followingunique characteristics of implants manufactured from this material:

1. Absorbable structural implants wherein strength and stiffnessproperties are anisotropic. The bending resistance and other mechanicalproperties of these implants depends greatly on the specific design ofthe part and of the alignment of reinforcing fibers within the part. Itis therefore possible to design such implants efficiently such that theyprovide sufficient support in the necessary axes (for example, flexuralstiffness) without comprising an excessive amount of material that wouldprovide equivalent support in the remaining axes (for example, tensilestiffness).2. Low profile/minimally invasive/material efficient design forabsorbable implant that take advantage of the strength and stiffnesscharacteristics of the reinforced absorbable composite material tocreate implants that achieve bone fixation with minimal profile. By“minimal profile”, it is meant that the implant is reduced in size in atleast one dimension in comparison with an equivalent currently availableimplant that is not made from such composite material.3. Load bearing absorbable bone implants, as opposed to previousabsorbable implants which did not approach the stiffness of corticalbone.4. Small functional features, such as anchors, ridges, teeth, etc thatrequire the reinforcement in order to be strong enough to be functional.Previous absorbable materials may not have had sufficient strength forsuch features.5. The capability of being produced according to fiber-reinforcedcomposite specific manufacturing techniques such as compression molding,pultrusion, etc.6. Reduced damage to surrounding tissues, including both soft tissuesand bone tissues, as compared with the trauma of stress risers or stressshielding that can arise from use of high modulus (such as metal)implants.

The present invention, according to at least some embodiments, thusprovides medical implants that are useful as structural fixation forload-bearing purposes, exhibiting sustained mechanical properties.

The present invention, according to at least some embodiments, furthercomprises a biodegradable composite material in which the drawbacks ofthe prior art materials can be minimized or even eliminated, i.e. thecomposite retains its strength and modulus in vivo for a time periodsufficient for bone healing for example. Mechanical strength as usedhere includes, but is not limited to, bending strength, torsionstrength, impact strength, compressive strength and tensile strength.

The presently claimed invention, in at least some embodiments, relate toa biocomposite material comprising a biocompatible polymer and aplurality of reinforcing fibers, wherein said reinforcing fibers areoriented in a parallel orientation.

The biocomposite material has one or more mechanical properties whichfeature an increased extent or degree as compared to such a materialwith reinforcing fibers oriented in a non-parallel orientation.Optionally such a non-parallel orientation is a perpendicular oramorphous (non-oriented) orientation, elastic modulus, tensile modulus,compression modulus, shear modulus, bending moment, moment of inertia,bending strength, torsion strength, shear strength, impact strength,compressive strength and/or tensile strength. The increased extent ordegree may optionally be at least twice as great, at least five times asgreat, at least ten times as great, at least twenty times as great, atleast fifty times as great, or at least a hundred times as much, or anyintegral value in between.

Optionally the mechanical properties can comprise any one of Flexuralstrength, Elastic modulus and Maximum load, any pair of same or all ofthem. Optionally density and/or volume are unchanged or are similarwithin 5%, within 10%, within 15%, within 20%, any integral value inbetween or any integral value up to 50%.

Optionally the biocomposite implant as described herein is swellable,having at least 0.5% swellability, at least 1%, 2% swellability, andless than 20% swellability, preferably less than 10% or any integralvalue in between.

Optionally, the swellability in one mechanical axis is greater than theswellability in a second mechanical axis. Preferably the difference inswelling percentage (%) between axes is at least 10%, at least 25%, atleast 50%, or at least 100%, or any integral value in between.

After exposure to biological conditions for 1 hour, 12 hours, 24 hours,48 hours, five days, one week, one month, two months or six months orany time value in between, the biocomposite material implants preferablyretain at least 10%, at least 20%, at least 50%, at least 60%, at least75%, at least 85% or up to 100% of flexural strength, Modulus and/or Maxload, and/or volume, or any integral value in between. By “biologicalconditions” it is meant that the temperature is between 30-40 C butpreferably is at 37 C. Optionally, fluid conditions replicate those inthe body as well, under “simulated body fluid” conditions.

The flexural strength of the implant or segment of the implant ispreferably at least 200 MPA, at least 400 mPa, at least 600 mPA, atleast 1000 mPA or any integral value in between.

Relevant implants may include bone fixation plates, intramedullarynails, joint (hip, knee, elbow) implants, spine implants, and otherdevices for such applications such as for fracture fixation, tendonreattachment, spinal fixation, and spinal cages.

According to at least some embodiments, there are provided medicalimplants for bone or soft tissue fixation comprising a biodegradablecomposite, wherein said composite optionally and preferably has thefollowing properties:

(i) wherein biodegradable composite comprises one or more biodegradablepolymers and a resorbable, reinforcement fiber; and

(ii) wherein one or more segments comprising the medical implant have amaximum flexural modulus in the range of 6 GPa to 30 GPa and flexuralstrength in the range of 100 MPa to 1000 MPa; and

(iii) wherein the average density of the composite is in the range of1.1-3.0 g/cm³.

Preferably, average density of the composite is in the range of 1.2-2.0g/cm³.

More preferably, average density of the composite is in the range of1.3-1.6 g/cm³.

Preferably, flexural modulus is in the range of 10 GPa to 28 GPa andmore preferably in the range of 15 to 25 GPa.

Preferably, flexural strength is in the range of 200-800 MPa. Morepreferably, 400-800 MPa.

In a preferred embodiment of the present invention, at least 50% ofelastic modulus is retained following exposure to simulated body fluid(SBF) at 50° C. for 3 days. More preferably at least 70% is retained,and even more preferably at least 80% is retained.

In a preferred embodiment of the present invention, at least 20% ofstrength is retained following exposure to simulated body fluid (SBF) at50° C. for 3 days. More preferably at least 30% is retained, and evenmore preferably at least 40% is retained.

In a preferred embodiment of the present invention, at least 50% ofelastic modulus is retained following exposure to simulated body fluid(SBF) at 37° C. for 3 days. More preferably at least 70%, and even morepreferably at least 85%.

In a preferred embodiment of the present invention, at least 30% ofstrength is retained following exposure to simulated body fluid (SBF) at37° C. for 3 days. More preferably at least 45%, and even morepreferably at least 60%.

Specifically regarding medical implants described herein that containone or more segments that can be anisotropic, this anisotropicityreflects a significant divergence from what has be previously acceptedin medical, and specifically orthopedic, implants in that theanisotropic structure results in implants in which there are mechanicalproperties in one or more axis that are less than the optimal mechanicalproperties which may be achieved by the materials from which the implantis comprised. In contrast, traditional implants have relied upon theuniform mechanical properties of the materials from which they arecomprised as this does not require compromising in any axis.

The anisotropic approach can only be applied following biomechanicalanalysis to determine that greater implant mechanical properties isrequired in certain axes as opposed to other axes. For example, animplant may be subjected to very high bending forces but only nominaltensile forces and therefore require a much greater emphasis on bendingforces. Other relevant axes of force in a medical implant can includetensile, compression, bending, torsion, shear, pull-out (from bone)force, etc.

There are several factors that affect the mechanical properties of animplant. As described above, material composition alone results in agenerally uniform or isotropic structure. Without wishing to be limitedby a closed list or a single hypothesis, within fiber-reinforcedbiocomposite medical implants, an anisotropic structure may result fromone or more of the following characteristics:

-   -   1. The weight ratio of reinforcing fibers to biopolymer.        Preferably this ratio is in the range of 1:1 to 3:1 and more        preferably 1.5:1 to 2.5:1.    -   2. The density of the medical implant (this characteristic is        also determined to some extent the ratio of reinforcing fiber to        polymer)    -   3. The diameter of reinforcing fiber. The average fiber diameter        is preferably between 5 and 50 μm. More preferably between 10-30        μm.    -   4. Length of fiber (continuous fiber, long fiber, short fiber).        Preferably, having continuous fiber reinforcement with fibers        that run across the entire implant.    -   5. The alignment of fibers or fiber layers. Preferably, in each        segment of the implant, a majority of fibers or fiber layers are        aligned or partially aligned with the axis that will be exposed        to the highest bending forces. If partially aligned, then        preferably within a 45° angle of the axis.    -   6. The number of fibers or fiber layers aligned in any given        direction. Preferably fiber layers are 0.1 to 1 mm in thickness        and more preferably 0.15 to 0.25 mm.    -   7. The order of fiber layers.

In one embodiment of the present invention, the medical implant is apin, screw, or wire.

Preferably, a pin or wire of 2 mm external diameter will have a shearload carrying capacity of greater than 200 N. More preferably shear loadcarrying capacity of 2 mm pin will exceed 400 N and most preferably willexceed 600 N.

Bioabsorbable Polymers

In a preferred embodiment of the present invention, the biodegradablecomposite comprises a bioabsorbable polymer.

The medical implant described herein may be made from any biodegradablepolymer. The biodegradable polymer may be a homopolymer or a copolymer,including random copolymer, block copolymer, or graft copolymer. Thebiodegradable polymer may be a linear polymer, a branched polymer, or adendrimer. The biodegradable polymers may be of natural or syntheticorigin. Examples of suitable biodegradable polymers include, but are notlimited to polymers such as those made from lactide, glycolide,caprolactone, valerolactone, carbonates (e.g., trimethylene carbonate,tetramethylene carbonate, and the like), dioxanones (e.g.,1,4-dioxanone), 6-valerolactone, 1, dioxepanones) e.g.,1,4-dioxepan-2-one and 1,5-dioxepan-2-one), ethylene glycol, ethyleneoxide, esteramides, γ-ydroxyvalerate, β-hydroxypropionate, alpha-hydroxyacid, hydroxybuterates, poly (ortho esters), hydroxy alkanoates,tyrosine carbonates, polyimide carbonates, polyimino carbonates such aspoly (bisphenol A-iminocarbonate) and poly (hydroquinone-iminocarbonate,(polyurethanes, polyanhydrides, polymer drugs (e.g., polydiflunisol,polyaspirin, and protein therapeutics (and copolymers and combinationsthereof. Suitable natural biodegradable polymers include those made fromcollagen, chitin, chitosan, cellulose, poly (amino acids),polysaccharides, hyaluronic acid, gut, copolymers and derivatives andcombinations thereof.

According to the present invention, the biodegradable polymer may be acopolymer or terpolymer, for example: polylactides (PLA), poly-L-lactide(PLLA), poly-DL-lactide (PDLLA); polyglycolide (PGA); copolymers ofglycolide, glycolide/trimethylene carbonate copolymers (PGA/TMC); othercopolymers of PLA, such as lactide/tetramethylglycolide copolymers,lactide/trimethylene carbonate copolymers, lactide/d-valerolactonecopolymers, lactide/ε-caprolactone copolymers, L-lactide/DL-lactidecopolymers, glycolide/L-lactide copolymers (PGA/PLLA),polylactide-co-glycolide; terpolymers of PLA, such aslactide/glycolide/trimethylene carbonate terpolymers,lactide/glycolide/ε-caprolactone terpolymers, PLA/polyethylene oxidecopolymers; polydepsipeptides; unsymmetrically-3,6-substitutedpoly-1,4-dioxane-2,5-diones; polyhydroxyalkanoates; such aspolyhydroxybutyrates (PHB); PHB/b-hydroxyvalerate copolymers (PHB/PHV);poly-b-hydroxypropionate (PHPA); poly-p-dioxanone (PDS);poly-d-valerolactone-poly-ε-capralactone,poly(ε-caprolactone-DL-lactide) copolymers; methylmethacrylate-N-vinylpyrrolidone copolymers; polyesteramides; polyesters of oxalic acid;polydihydropyrans; polyalkyl-2-cyanoacrylates; polyurethanes (PU);polyvinylalcohol (PVA); polypeptides; poly-b-malic acid (PMLA):poly-b-alkanbic acids; polycarbonates; polyorthoesters; polyphosphates;poly(ester anhydrides); and mixtures thereof; and natural polymers, suchas sugars; starch, cellulose and cellulose derivatives, polysaccharides,collagen, chitosan, fibrin, hyalyronic acid, polypeptides and proteins.Mixtures of any of the above-mentioned polymers and their various formsmay also be used.

The biodegradable composite is preferably embodied in a polymer matrix,which may optionally comprise any of the above polymers. Optionally andpreferably, it may comprise a polymer selected from the group consistingof a bioabsorbable polyester, PLLA (poly-L-lactide), PDLLA(poly-DL-lactide), PLDLA, PGA (poly-glycolic acid), PLGA(poly-lactide-glycolic acid), PCL (Polycaprolactone), PLLA-PCL and acombination thereof. If PLLA is used, the matrix preferably comprises atleast 30% PLLA, more preferably 50%, and most preferably at least 70%PLLA. If PDLA is used, the matrix preferably comprises at least 5% PDLA,more preferably at least 10%, most preferably at least 20% PDLA.

Optionally, the inherent viscosity (IV) of the polymer matrix(independent of the reinforcement fiber) is in the range of 0.2-6 dl/g,preferably 1.0 to 3.0 dl/g, more preferably in the range of 1.5 to 2.4dl/g, and most preferably in the range of 1.6 to 2.0 dl/g.

Inherent Viscosity (IV) is a viscometric method for measuring molecularsize. IV is based on the flow time of a polymer solution through anarrow capillary relative to the flow time of the pure solvent throughthe capillary.

Reinforced Biocomposite

According to at least some embodiments of the present invention, themedical implant comprises a reinforced biocomposite (i.e. abioabsorbable composite that includes the previously described polymerand also incorporates a reinforcing filler, generally in fiber form, toincrease the mechanical strength of the polymer). For the avoidance ofdoubt, the terms “filler” and “fiber” are used interchangeably todescribe the reinforcing material structure.

In a more preferred embodiment of the present invention, the reinforcedbioabsorbable polymer is a reinforced polymer composition comprised ofany of the above-mentioned bioabsorbable polymers and a reinforcingfiller, preferably in fiber form. The reinforcing filler may becomprised of organic or inorganic (that is, natural or synthetic)material. Reinforcing filler may be a biodegradable glass or glass-likematerials, a ceramic, a mineral composition (optionally including one ormore of hydroxyapatite, tricalcium phosphate, calcium sulfate, calciumphosphate), a cellulosic material, a nano-diamond, or any other fillerknown in the art to increase the mechanical properties of abioabsorbable polymer. The filler may also optionally be a fiber of abioabsorbable polymer itself. Preferably, reinforcing fiber is comprisedof a bioabsorbable glass, ceramic, or mineral composition.

Preferably, reinforcement fiber is comprised of silica-based mineralcompound such that reinforcement fiber comprises a bioresorbable glassfiber, which can also be termed a bioglass fiber composite.

According to at least some embodiments, bioresorbable glass fiber mayoptionally have oxide compositions in the following mol. % ranges (as apercent over the glass fiber composition):

Na₂O: 11.0-19.0 mol. %

CaO: 9.0-14.0 mol. %

MgO: 1.5-8.0 mol. %

B₂O₃: 0.5-3.0 mol. %

Al₂O₃: 0-0.8 mol. %

P₂O₃: 0.1-0.8 mol. %

SiO₂: 67-73 mol. %

but preferably preferably in the following mol. % ranges:

Na₂O: 12.0-13.0 mol. %

CaO: 9.0-10.0 mol. %

MgO: 7.0-8.0 mol. %

B₂O₃: 1.4-2.0 mol. %

P₂O₃: 0.5-0.8 mol. %

SiO₂: 68-70 mol. %

Additional optional bioresorbable glass compositions are described inthe following patent applications, which are hereby incorporated byreference as if fully set forth herein: Biocompatible composite and itsuse (WO2010122098); and Resorbable and biocompatible fibre glasscompositions and their uses (WO2010122019).

Tensile strength of the reinforcement fiber is preferably in the rangeof 1200-2800 MPa, more preferably in the range of 1600-2400 MPa, andmost preferably in the range of 1800-2200 MPa.

Elastic modulus of the reinforcement fiber is preferably in the range of30-100 GPa, more preferably in the range of 50-80 GPa, and mostpreferably in the range of 60-70 GPa.

Reinforcing filler is preferably incorporated in the bioabsorbablepolymer matrix of the biocomposite in fiber form. Preferably, suchfibers are continuous fibers.

Preferably continuous fibers are aligned within the implant such thatthe ends of fibers don't open at the surface of the implant.

Preferably, fibers are distributed evenly within the implant.

Specifically within bioabsorbable fiber-reinforced composites, achievingthe high strengths and stiffness required for many medical implantapplications can require the use of continuous-fiber reinforcementrather than short or long fiber reinforcement. This creates asignificant difference from the implant structures, architectures,designs, and production techniques that have been previously used withmedical implants produced from polymers or composites comprising shortor long fiber reinforced polymers. Those implants are most commonlyproduced using injection molding, or occasionally 3-D printing,production techniques. The production of these implants generallyinvolves homogeneity of the material throughout the implant and thefinished implant is then comprised of predominantly isotropic material.However, with continuous fiber-reinforcement, the fibers must becarefully aligned such that each fiber or bundle of fibers runs along apath within the composite material such that they will providereinforcement along specific axes within the implant to provide stressresistance where it is most needed.

The present invention provides, in at least some embodiments, implantcompositions from continuous-fiber reinforced bioabsorbable compositematerials that are a significant step forward from previousbioabsorbable implants in that they can achieve sustainably high, loadbearing strengths and stiffness. Additionally, many embodiments of thepresent invention additionally facilitate these high strength levelswith efficient implants of low volume since the anisotropic nature ofthe implants can allow the implants to achieve high mechanicalproperties in axes where those properties are needed (for example inbending resistance) without necessitating the additional volume thatwould be needed to uniformly provide high mechanical properties in allother axes.

According to at least some embodiments, there is provided a medicalimplant comprising a plurality of composite layers, said layerscomprising a biodegradable polymer and a plurality of uni-directionallyaligned continuous reinforcement fibers. Optionally and preferably, thebiodegradable polymer is embodied in a biodegradable composite. Alsooptionally and preferably, the fibers are embedded in a polymer matrixcomprising one or more bioabsorbable polymers.

According to at least some embodiments, the composite layers are eachcomprised of one or more composite tapes, said tape comprising abiodegradable polymer and a plurality of uni-directionally alignedcontinuous reinforcement fibers. Optionally and preferably, thebiodegradable polymer is embodied in a biodegradable composite. Alsooptionally and preferably, the fibers are embedded in a polymer matrixcomprising one or more bioabsorbable polymers.

Preferably, the composite tape layer comprises reinforcement fibers thatare pre-impregnated with polymer.

Preferably, each composite layer is of thickness 0.05 mm-0.5 mm, morepreferably 0.15-0.35 mm, and most preferably 0.1-0.25 mm.

Preferably, each composite tape is of width 2-30 mm, more preferablytape is of width 4-16 mm, and most preferably of width 6-12 mm.

Preferably, reinforcement fiber content within the composite tape is inthe range of 20-70%, more preferably in the range of 30-60%, morepreferably in the range of 40-50%, and most preferably 45-50% over theentire composite tape materials.

Optionally and preferably, the fiber-reinforced biodegradable compositewithin the implant has a flexural modulus exceeding 10 GPa and flexuralstrength exceeding 100 MPa.

Optionally, the fiber-reinforced biodegradable composite within theimplant has flexural strength in range of 200-1000 MPa, preferably300-800 MPa, more preferably in the range of 400-800 MPa, and mostpreferably in the range of 500-800 MPa

Optionally, the fiber-reinforced biodegradable composite within theimplant has elastic modulus in range of 10-30 GPa, preferably 12-28 GPa,more preferably in the range of 16-28 GPa, and most preferably in therange of 20-26 GPa.

Optionally, fibers may be aligned at an angle to the longitudinal axis(i.e. on a diagonal) such that the length of the fiber may be greaterthan 100% of the length of the implant. Optionally and preferably, amajority of reinforcement fibers are aligned at an angle that is lessthan 90°, alternatively less than 60°, or optionally less than 45° fromthe longitudinal axis.

Preferably, the implant preferably comprises between 2-20 composite tapelayers, more preferably between 2-10 layers, and most preferably between2-6 layers; wherein each layer may be aligned in a different directionor some of the layers may be aligned in the same direction as the otherlayers.

Preferably, the maximum angle between fibers in at least some of thelayers is greater than the angle between the fibers in each layer andthe longitudinal axis. For example, one layer of reinforcing fibers maybe aligned and a right diagonal to the longitudinal axis while anotherlayer may be aligned at a left diagonal to the longitudinal axis.

Optionally and preferably, the composite composition additionallyincludes a compatibilizer, which for example be such an agent asdescribed in WO2010122098, hereby incorporated by reference as if fullyset forth herein.

Reinforcing fiber diameter preferably in range of 2-40 um, preferably8-20 um, most preferably 12-18 um (microns).

Preferably, the implant includes only one composition of reinforcingfiber.

Preferably fibers don't open at the surface of the implant.

Numerous examples of reinforced polymer compositions have previouslybeen documented. For example: A biocompatible and resorbable meltderived glass composition where glass fibers can be embedded in acontinuous polymer matrix (EP 2 243 749 A1), Biodegradable compositecomprising a biodegradable polymer and 20-70 vol % glass fibers(WO2010128039 A1), Resorbable and biocompatible fiber glass that can beembedded in polymer matrix (US 2012/0040002 A1), Biocompatible compositeand its use (US 2012/0040015 A1), Absorbable polymer containingpoly[succinimide] as a filler (EPO 671 177 B1).

In a more preferred embodiment of the present invention, the reinforcingfiller is covalently bound to the bioabsorbable polymer such that thereinforcing effect is maintained for an extended period. Such anapproach has been described in US 2012/0040002 A1 and EP 2243500B1,hereby incorporated by reference as if fully forth herein, whichdiscusses a composite material comprising biocompatible glass, abiocompatible matrix polymer and a coupling agent capable of formingcovalent bonds.

Fabrication of the Implant

Any of the above-described bioabsorbable polymers or reinforcedbioabsorbable polymers may be fabricated into any desired physical formfor use with the present invention. The polymeric substrate may befabricated for example, by compression molding, casting, injectionmolding, pultrusion, extrusion, filament winding, composite flow molding(CFM), machining, or any other fabrication technique known to thoseskilled in the art. The polymer may be made into any shape, such as, forexample, a plate, screw, nail, fiber, sheet, rod, staple, clip, needle,tube, foam, or any other configuration suitable for a medical device.

Load-Bearing Mechanical Strength

The present invention particularly relates to bioabsorbable compositematerials that can be used in medical applications that require highstrength and a stiffness compared to the stiffness of bone. Thesemedical applications require the medical implant to bear all or part ofthe load applied by or to the body and can therefore be referred togenerally as “load-bearing” applications. These include bone fixation,fracture fixation, tendon reattachment, joint replacement, spinalfixation, and spinal cages.

The flexural strength preferred from a bioabsorbable composite (such asa reinforced bioabsorbable polymer) for use in the load-bearing medicalimplant is at least 200 MPa, preferably above 400 MPa, more preferablyabove 600 MPa, and even more preferably above 800 MPa. The ElasticModulus (or Young's Modulus) of the bioabsorbable composite for use withpresent invention is preferably at least 10 GPa, more preferably above15 GPa, and even more preferably above 20 GPa but not exceeding 100 GPaand preferably not exceeding 60 GPa.

Sustained Mechanical Strength

There is a need for the bioabsorbable load-bearing medical implants ofthe present invention to maintain their mechanical properties (highstrength and stiffness) for an extended period to allow for sufficientbone healing. The strength and stiffness preferably remains above thestrength and stiffness of cortical bone, approximately 150-250 MPa and15-25 GPa respectively, for a period of at least 3 months, preferably atleast 6 months, and even more preferably for at least 9 months in vivo(i.e. in a physiological environment).

More preferably, the flexural strength remains above 400 MPa and evenmore preferably remains above 600 MPa.

The present invention overcomes the limitations of previous approachesand provides medical implants comprised of biodegradable compositionsthat retain their high mechanical strength and stiffness for an extendedperiod sufficient to fully support bone regeneration and rehabilitation.

“Biodegradable” as used herein is a generalized term that includesmaterials, for example polymers, which break down due to degradationwith dispersion in vivo. The decrease in mass of the biodegradablematerial within the body may be the result of a passive process, whichis catalyzed by the physicochemical conditions (e.g. humidity, pH value)within the host tissue. In a preferred embodiment of biodegradable, thedecrease in mass of the biodegradable material within the body may alsobe eliminated through natural pathways either because of simplefiltration of degradation by-products or after the material's metabolism(“Bioresorption” or “Bioabsorption”). In either case, the decrease inmass may result in a partial or total elimination of the initial foreignmaterial. In a preferred embodiment, said biodegradable compositecomprises a biodegradable polymer that undergoes a chain cleavage due tomacromolecular degradation in an aqueous environment.

A polymer is “absorbable” as described herein if it is capable ofbreaking down into small, non-toxic segments which can be metabolized oreliminated from the body without harm. Generally, absorbable polymersswell, hydrolyze, and degrade upon exposure to bodily tissue, resultingin a significant weight loss. The hydrolysis reaction may beenzymatically catalyzed in some cases. Complete bioabsorption, i.e.complete weight loss, may take some time, although preferably completebioabsorption occurs within 24 months, most preferably within 12 months.

The term “polymer degradation” means a decrease in the molecular weightof the respective polymer. With respect to the polymers, which arepreferably used within the scope of the present invention saiddegradation is induced by free water due to the cleavage of ester bonds.The degradation of the polymers as for example used in the biomaterialas described in the examples follows the principle of bulk erosion.Thereby a continuous decrease in molecular weight precedes a highlypronounced mass loss. Such loss of mass is attributed to the solubilityof the degradation products. Methods for determination of water inducedpolymer degradation are well known in the art such as titration of thedegradation products, viscometry, differential scanning calorimetry(DSC).

Bulk degradation refers to a process of degradation in which there is atleast some perfusion of fluid through the material that is beingdegraded, such as the body of the implant, thereby potentially degradingthe bulk of the material of the implant (as opposed to the externalsurface alone). This process has many effects. Without wishing to belimited to a closed list, such bulk degradation means that simply makingan implant larger or thicker may not result in improved retainedstrength.

Surface degradation refers to a process of degradation in which theexternal surface undergoes degradation. However, if there is little orno perfusion of fluid through the material that is being degraded, thenthe portion of the implant that is not on the surface is expected tohave improved retained strength over implants in which such perfusionoccurs or occurs more extensively.

Clinical Applications

The medical implants discussed herein are generally used for bonefracture reduction and fixation to restore anatomical relationships.Such fixation optionally and preferably includes one or more, and morepreferably all, of stable fixation, preservation of blood supply to thebone and surrounding soft tissue, and early, active mobilization of thepart and patient.

There are several exemplary, illustrative, non-limiting types of bonefixation implants for which the materials and concepts describedaccording to at least some embodiments of the present invention may berelevant, as follows:

Screws

Screws are used for internal bone fixation and there are differentdesigns based on the type of fracture and how the screw will be used.Screws come in different sizes for use with bones of different sizes.Screws can be used alone to hold a fracture, as well as with plates,rods, or nails. After the bone heals, screws may be either left in placeor removed.

Screws are threaded, though threading can be either complete or partial.Screws can include compression screws, locking screws, and/or cannulatedscrews. External screw diameter can be as small as 0.5 or 1.0 mm but isgenerally less than 3.0 mm for smaller bone fixation. Larger bonecortical screws can be up to 5.0 mm and cancellous screws can even reach7-8 mm. Some screws are self-tapping and others require drilling priorto insertion of the screw. For cannulated screws, a hollow section inthe middle is generally larger than 1 mm diameter in order toaccommodate guide wires.

Wires/Pins

Wires are often used to pin bones back together. They are often used tohold together pieces of bone that are too small to be fixed with screws.They can be used in conjunction with other forms of internal fixation,but they can be used alone to treat fractures of small bones, such asthose found in the hand or foot. Wires or pins may have sharp points oneither one side or both sides for insertion or drilling into the bone.

“K-wire” is a particular type of wire generally made from stainlesssteel, titanium, or nitinol and of dimensions in the range of 0.5-2.0 mmdiameter and 2-25 cm length. “Steinman pins” are general in the range of2.0-5.0 mm diameter and 2-25 cm length. Nonetheless, the terms pin andwire for bone fixation are used herein interchangeably.

Anchors

Anchors and particularly suture anchors are fixation devices for fixingtendons and ligaments to bone. They are comprised of an anchormechanism, which is inserted into the bone, and one or more eyelets,holes or loops in the anchor through which the suture passes. This linksthe anchor to the suture. The anchor which is inserted into the bone maybe a screw mechanism or an interference mechanism. Anchors are generallyin the range of 1.0-6.5 mm diameter

Cable, Ties, Wire Ties

Cables, ties, or wire ties (one example of wire tie is Synthes ZipFix™)can be used to perform fixation by cerclage, or binding, bones together.Such implants may optionally hold together bone that cannot be fixatedusing penetration screws or wires/pin, either due to bone damage orpresence of implant shaft within bone. Generally, diameter of such cableor tie implants is optionally in the range of 1.0 mm-2.0 mm andpreferably in the range of 1.25-1.75 mm. Wire tie width may optionallybe in the range of 1-10 mm.

Nails or Rods

In some fractures of the long bones, medical best practice to hold thebone pieces together is through insertion of a rod or nail through thehollow center of the bone that normally contains some marrow. Screws ateach end of the rod are used to keep the fracture from shortening orrotating, and also hold the rod in place until the fracture has healed.Rods and screws may be left in the bone after healing is complete. Nailsor rods for bone fixation are generally 20-50 cm in length and 5-20 mmin diameter (preferably 9-16 mm). A hollow section in the middle of nailor rod is generally larger than 1 mm diameter in order to accommodateguide wires.

Other non-limiting, illustrative examples of bone fixation implants mayoptionally include plates, plate and screw systems, and externalfixators.

Any of the above-described bone fixation implants may optionally be usedto fixate various fracture types including but not limited to comminutedfractures, segmental fractures, non-union fractures, fractures with boneloss, proximal and distal fractures, diaphyseal fractures, osteotomysites, etc.

Bending Resistance

The primary mechanical challenge to wires or pins used for bone fixationis providing mechanical support (i.e. bending resistance) underbending/flexural stress to prevent the stress from creating a gapbetween the bone surfaces in the fracture which can prevent good bonehealing. For absorbable bone fixation implants, it is desirable for theimplant to provide bending resistance such that the implant deflects asimilar amount or less than the bones which it is fixating when exposedto bending stress. It is further desirable for the implant to providethis bending resistance with the minimal profile (i.e. minimal amount ofmaterial) in order to minimize the amount of degradation products overtime and also to reduce implant cost.

For a wire or pin, the amount of deflection it undergoes when subjectedto a flexural stress is directly related to (i) the flexural modulus ofthe material of which the implant is made; and (ii) the second moment ofinertia of the cross-section of the wire or pin across the axis acrosswhich the flexural stress is being applied.

Second moment of inertia refers to the property of a shape that directlycorrelates to its ability to resist bending and deflection. Secondmoment of inertia can alternatively be referred to as second moment ofarea, moment of inertia of plane area, area moment of inertia, polarmoment of area or second area moment.

In a preferred embodiment of the present invention, the elastic modulusof the implant or a segment of the implant as measured withflexural/bending testing is greater than the elastic modulus of theimplant or a segment of the implant as measured with tensile testing.Preferably, the difference is greater than 5%, more preferred thedifference is greater than 10%, even more preferred greater than 20%,30%, 40%, 50%.

In a preferred embodiment of the present invention, the flexural/bendingstrength of the implant is greater than its tensile or compressivestrength. In a more preferred embodiment, this difference is greaterthan 5%. Even more preferred, the higher flexural/bending strength ascompared with tensile or compressive strength is greater by at least10%, 30%, 50%, 70%, and most preferably 100%.

In an optional embodiment, the anisotropic nature of the medicalimplants described according to at least some embodiments of the presentinvention result in the mechanical properties in the bending axis thatare superior to the mechanical properties in the tensile or compressiveaxis. This difference can be at least partially determined by thealignment, orientation, or structure of reinforcing fibers with thebioabsorbable polymer matrix, as described in more detail above.

In a hollow tube geometry, its flexural/bending stiffness is relativelygreater than its tensile stiffness. The flexural stiffness is relativeto the second moment of inertia around the axis of bending, for examplethe second moment of inertia around the midline axis of a squarepin/beam is Ix=bh3/12 and for a hollow circular pin/beam,Ix=π(do4−di4)/64. Conversely, the tensile stiffness is relative to thecross-sectional area, A=bh for a square pin/beam and A=π(do2−di2)/4 fora hollow circular pin/beam.

In a preferred embodiment of the present invention, one or more voidsare present within the implant, such that the second moment of inertiaof the cross-section of the wire or pin across the mid-line axis of theimplant is less than the second moment of inertia for such a part withthe same or similar external dimensions but a void-less (i.e. whole orsolid) cross-sectional area. Preferably, the reduction in the secondmoment of inertia is smaller than 30%, more preferably 20% and mostpreferably 10% than for a solid part.

Alternatively, a wire or pin may comprise open space between differentstruts, ribs, arms, etc of the wire or pin such that wire or pin formsan asterisk type cross-section thereby similarly providing increasedrelative flexural stiffness in relation to its tensile stiffness.

Preferably, the average cross-sectional area of the wire or pin isreduced by a greater percentage than the average second moment ofinertia of its cross-section as compared to a solid part with similardimensions as previously described. More preferably, the cross-sectionalarea is more than 20% smaller while the second moment of inertia isreduced by less than 20%. Even more preferably, the cross-sectional areais more than 20% smaller while the second moment of inertia is reducedby less than 10%.

Dimensions

For orthopedic implants, it is desirable for the implant to have aminimal profile so as to allow for implantation with minimal soft tissuedamage. Furthermore, it is preferable to produce the implant withsufficient robustness to provide necessary mechanical strength butotherwise not contain extraneous material.

In a preferred embodiment of the present invention, the externaldiameter of the wire or pin is less than 15 mm, more preferably lessthan 10 mm, even more preferably less than 5 mm and most preferably lessthan 3 mm.

In a preferred embodiment of the present invention, the wall thicknessof the wire or pin is less than 5 mm, more preferably less than 3 mm,even more preferably less than 1 mm and most preferably less than 0.7mm.

Voids in Implant

As described above, it may be desirable to have a wire or pin that ishollow in order to provide bending resistance with the most efficientamount of material. Nonetheless, there are potential complicationsinvolved in implanting a hollow implant in bone, as non-bone tissuecells, such as fibroblasts, can penetrate into the hollow void andthereby impede or slow regeneration of bone in that area.

In a preferred embodiment of the present invention, the wire or pincontains a hollow section or void internally but such void is coveredsuch that cells cannot invade void prior to degradation of implantmaterial.

In another embodiment of the present invention, the hollow section canbe filled with active ingredients such as antibiotics, growth factors orbone filler to prevent such invasion.

In another embodiment hollow section can be used to introduce activeingredients into fracture area via holes in the wall of the hollow wireor pin.

Example #1

The below example describes the extent to which the anisotropic natureof the herein described reinforced biocomposite implants impacts themechanical properties of the implants. Depending on the mechanicalproperty parameter, the differences in the degree of anisotropicity in amedical implant or medical implant part can reach even 5× or greater.Without wishing to be limited by a single hypothesis, these differencesmay be due to differences between alignments of reinforcing fiberswithin the implant.

Materials and Methods

Rectangular testing samples (dimensions 50.8 mm×12.7 mm×1 mm),simulating plates used for small bone fixation, were produced usingreinforced composite material. Material composite was comprised of PLDLA70/30 polymer reinforced with 40%-50% w/w continuous mineral fibers.Mineral fibers were as described for composition “NX-8” in Lehtonen T Jet al. Acta Biomaterialia 9 (2013) 4868-4877. Mineral composition wasspecifically approximately Na2O 14%, MgO 5.4%, CaO 9%, B2O3 2.3%, P2O51.5%, and SiO2 67.8% w/w. All testing samples were from one plate,manufactured by compression molding of five layers of compositematerial, each comprised of the PLDLA polymer with embeddeduni-directionally aligned continuous fibers. Each layer was 0.18 mmthick.

In four samples, orientation of layers relative to longitudinal axis ofimplant were 0° (parallel to implant longitudinal axis), 45°, 0°, −45°,0°. In four other samples, orientation of layers relative tolongitudinal axis were 90° (perpendicular to implant longitudinal axis),−45°, 90°, 45°, 90°.

Implant samples were tested for Flexural strength, Elastic modulus andMaximum load according to ASTM D790-10 with a 500N load cell and a 3point bending fixture (220Q1125-95, TestResources, MN, USA). Load spanwas 25.4 mm and cross head speed was set at 1.092 mm/min. Dimensions,weight and density of samples were measured. Statistical comparisonbetween two treatments was performed using a t-test. A confidence levelof p=0.05 was used.

Results

FIG. 2 shows the anisotropic properties of a bio-composite plate asdemonstrated by the large difference in mechanical properties of sampleswith identical compositions, but with a majority of layers aligned ateither 0° (Parallel) or 90° (Perpendicular) to the longitudinal axis ofthe implant sample (n=4). The numerical results are summarized in Table1.

TABLE 1 Mean values and standard deviations of statistically significantmechanical properties of the anisotropic implants. (n = 4). Density andVolume of the different samples were similar. Flexural Max DensityVolume E [MPa] Strength [MPa] Load [N] [gr/ml] [mm³] Perpendicular1524.4 ± 281 45.9 ± 1.6 12.4 ± 1.4 1.48 ± 0.01 662.1 ± 32.3 Parallel9795.4 ± 610 235.4 ± 25.4 81.4 ± 7.7 1.49 ± 0.03 694.0 ± 19.3Anisotropicity [%] 642.6 512.8 656.3 [Par/perp * 100]

FIG. 3 shows representative examples of samples. FIG. 3A shows a samplewith majority of layers with fiber orientation perpendicular to implantlongitudinal axis. FIG. 3B shows a sample with majority of layers withfiber orientation parallel to implant longitudinal axis. The mechanicalproperties of sample B were superior to those of sample A.Anisotropicity of mechanical properties in this example was more than500%. The anisotropocity was calculated as a percentage by dividing eachof the mechanical parameter values as measured for the samples withperpendicular (tranverse) fiber alignment by the corresponding value asmeasured for the samples with parallel fiber alignment.

Example #2

The below example describes the extent to which the anisotropic natureof the herein described reinforced biocomposite implants impacts themechanical properties of the implants. This example additionally showsthat an implant comprised of a randomly distributed, or amorphous,composition of reinforced biocomposite materials will have far inferiormechanical properties in the desired axis to the herein describedanisotropic medical implant with alignment of reinforcing fibers thatmaximizes the mechanical properties in the desired axis (in this case,bending force).

The example also demonstrates anisotropicity in that the modulus, whenmeasured by flexural testing, can be either higher or lower than thetensile modulus of the same part depending on the directionality of theflexural test.

Materials and Methods

Rectangular testing samples (dimensions 50.8 mm×12.7 mm×0.7 mm),simulating plates used for small bone fixation, were produced usingreinforced composite material. Material composite was as described inExample 1.

16 testing samples were produced, manufactured by compression molding offour layers of composite material. Each layer was 0.18 mm thick. In foursamples, samples were each comprised of the PLDLA polymer with embeddeduni-directionally aligned continuous fibers where orientation of layersrelative to longitudinal axis of implant were 0° (parallel to implantlongitudinal axis), 0°, 0°, 0°. In four other samples, orientation oflayers relative to longitudinal axis were 90°(perpendicular to implantlongitudinal axis), 90°, 90°, 90°. In four other samples, the continuousfiber embedded layers were not uni-directionally aligned but rather thelayers were chopped into segments of approximately 3 mm and then moldedtogether into the rectangular plates in bulk. In other words, thecomposition of these last four samples was identical to that of thecontinuous fiber groups but the material was used with random alignment,hereafter referred to as an “amorphous” form.

12 implant samples were tested for Flexural strength, Elastic modulusand Maximum load according to ASTM D790-10 with a 500N load cell and a 3point bending fixture (220Q1125-95, TestResources, MN, USA). Load spanwas 25.4 mm and cross head speed was set at 1.47 mm/min (1.71 mm/min foramorphous plates due to thinner dimension). Dimensions, weight anddensity of samples were measured. 4 implant samples (n=4) were testedfor tensile strength, tensile modulus and maximum load according tomodified ASTM D3039M with a 5 KN load cell and an appropriate fixture(220Q1125-95, TestResources, MN, USA). Sample span was 30 mm at thebeginning of the test and cross head speed was set at 2 mm/min.Dimensions, weight and density of samples were recorded.

Results

FIG. 4 shows that the anisotropic properties of a bio-composite plateare directly affected by fiber orientation, as demonstrated by the largedifference in mechanical properties of samples with identicalcompositions, but with non-aligned layers (Amorphous) or with layersaligned at either 0° (Parallel) or 90° (Perpendicular) to thelongitudinal axis of the implant sample (n=4). Table 2 summarizes thenumerical results for mechanical properties;

TABLE 2 Mean values and standard deviations of statistically significantmechanical properties of the anisotropic implants. (n = 4). Flexural MaxLoad Density E [Mpa] Strength [Mpa] [N] [gr/ml] Volume [mm³] Amorphous3183.15 ± 396.7 56.56 ± 6.2  6.10 ± 0.73 1.46 ± 0.05  405.50 ± 49Parallel 10572.5 ± 878.2 333.1 ± 32.8 41.74 ± 6.17  1.34 ± 0.066 447.67± 21 Perpendicular 483.47 ± 84.4 14.22 ± 0.76 2.13 ± 0.13 1.33 ± 0.021  487.26 ± 18.3 Parallel to 332% 589% 684% Amorphous Anisotropocity (%)Parallel to 2189%  2342%  1960%  Perpendicular Anisotropocity (%)Amorphous to 659% 398% 286% Perpendicular Anisotropocity (%)

TABLE 3 Mean values and standard deviations of tensile mechanicalproperties of the implants (n = 4). Tensile Ultimate Strength tensilestrain Tensile Max Density Volume E [MPa] [MPa] [mm/mm] Load [N] [gr/ml][mm3] Tensile Plate (Parallel) 7700.35 ± 594.7 89.65 ± 6.71 0.075 ± 0.01752.5 ± 94.8 1.47 ± 0.03 428.66 ± 48.9 Improvement in mechanical 137%372% properties as tested in flexural axis as compared with mechanicalproperties as tested in tensile axis (% of flexural value divided bytensile value)

FIG. 5 shows representative sample examples. FIG. 5A shows an amorphousfiber orientation sample; FIG. 5B shows a sample with majority of layerswith fiber orientation perpendicular to implant longitudinal axis. FIG.5C shows a sample with majority of layers with fiber orientationparallel to implant longitudinal axis. Mechanical properties of sample Cwere superior to those of samples A and B; however sample A hadproperties that were superior to sample B, presumably due to thepresence of at least some parallel fibers.

Example #3

Example 3 differs from Examples 1 and 2 in that identical materialcomposites were used to produce rectangular plate implants but adifferent production method was used that resulted in a lower density.This examples shows that such samples with lower density have muchinferior mechanical properties as compared with the otherwise similarhigher density samples described in examples 1 and 2. Density changesare due to the production method. Without wishing to be limited by asingle hypothesis, density depends on how much air or water isincorporated in the implant over the course of production.

Materials and Methods

Rectangular testing samples (dimensions 50.8 mm×12.7 mm×1.1 mm),simulating plates used for small bone fixation, were produced usingreinforced composite material. Material composite was as described inExample 1.

Four testing samples were produced, manufactured by a two step processof 1) wrapping two complete layers of composite material around a 40 mmdiameter tube using a hot air blower to adhere layers to each other andform a two layer biocomposite tube; 2) cutting biocomposite tube intotwo sheets and pressing sheets against each other using heated steelblocks. Each layer was 0.18 mm thick. The resulting samples were eachcomprised of the PLDLA polymer with embedded uni-directionally alignedcontinuous fibers where orientation of layers relative to longitudinalaxis of implant were 8°, −8°, 8°, −8°. This specific alignment wasdesigned to approximate 0° and would be expected to approximate themechanical properties of the 0° (Parallel) samples described in example2 if all other parameters were equal.

Implant samples were tested for Flexural strength, Elastic modulus andMaximum load according to ASTM D790-10 with a 500N load cell and a 3point bending fixture (220Q1125-95, TestResources, MN, USA). Load spanwas 25.4 mm and cross head speed was set at 0.942 mm/min (Dimensions,weight and density of samples were measured. Statistical comparisonbetween two treatments was performed using a t-test. A confidence levelof p=0.05 was used.

Results

Table 4 shows the significance of structural differences betweenreinforced composites. The alignment with 8 degree fiber offsetdescribed herein would be expected to be nearly identical to theparallel fiber alignment described in Example 1, and yet the strengthand modulus are drastically lower. Without wishing to be limited by asingle hypothesis, it is believed that the much lower density seen inthis example (Example 3) was the cause or at least a significantlycontributing factor.

TABLE 4 Mean values and standard deviations of the mechanical propertiesof the anisotropic implant. (n = 4). Flexural Strength Max Load DensityVolume E [MPa] [MPa] [N] [gr/ml] [mm³] 4 layers, 8 deg 2052.47 ± 96.5549.24 ± 2 18.52 ± 0.43 0.935 ± 0.01 775.49 ± 17.11

Example #4

The below example describes how anisotropic biocomposite implants retainsignificant mechanical properties (modulus and strength) after exposureto rigorous accelerated degradation conditions.

Materials and Methods

Rectangular testing samples (dimensions 50.8 mm×12.7 mm×1.1 mm),simulating plates used for small bone fixation, were produced usingreinforced composite material. Material composite was as described inExample 1.

Eight testing samples were produced, manufactured by compression moldingof four or five layers of composite material. Each layer was 0.18 mmthick. In four samples, five layer samples were each comprised of thePLDLA polymer with embedded uni-directionally aligned continuous fiberswhere orientation of layers relative to longitudinal axis of implantwere 0° (parallel to implant longitudinal axis), 45°, 0°, −45°, 0°. Infour other samples, four layer samples were each comprised of the PLDLApolymer with embedded uni-directionally aligned continuous fibers whereorientation of layers relative to longitudinal axis were 0° (parallel toimplant longitudinal axis), 45°, −45°, 0°.

Implant samples were tested for Flexural strength, Elastic modulus andMaximum load according to ASTM D790-10 with a 500N load cell and a 3point bending fixture (220Q1125-95, TestResources, MN, USA). Load spanwas 25.4 mm and cross head speed was set at 1.536 mm/min. Implants weretested either at time=0 or after incubation in simulated body fluid(SBF). SBF was comprised of: 142 Na+, 5 K+, 1.5 Mg 2+, 2.5 Ca2+, 147.8Cl−, 4.2 HCO3−, 1 HPO43−, 0.5 SO4 2− mol/m3. Samples were incubated ateither 60 or 50 degrees C. in a shaking incubator (Wis-30 shakingincubator, Witeg, Germany) at 30 rpm for 3-4 days.

Results

FIGS. 6 and 7: After exposure to accelerated degradation conditions of50° C. for three days, both groups of samples retained >80% of theirelastic modulus and >30% of their flexural strength. 50° C. is thehighest indicative temperature for incubation conditions for accelerateddegradation since the Tg of the biocomposite material is ^(˜)56 C.) FIG.6 shows elastic modulus after exposure to forced degradation, while FIG.7 shows flexural strength after exposure to forced degradation.

Example #5

Below example describes production of hollow pin implants withreinforced biocomposite materials. As with plates, hollow pins withalignment with anisotropic characteristics, result in higher mechanicalproperties in the desired bending force parameters.

Materials and Methods

Hollow pin implants of dimensions appropriate for small bone fixation (2mm OD, 1 mm ID, 5 cm) were made of composite material of composition asdescribed in Example 1. Pin implants were manufactured in two steps andtwo types of pin implants were produced: Parallel alignment andamorphous alignment.

For parallel alignment samples (n=7), plates of 0.5-0.6 mm were producedby compression molding three 0.18 mm thick layers of biocompositematerial. Plates were each comprised of the PLDLA polymer with embeddeduni-directionally aligned continuous fibers where orientation of layersrelative to longitudinal axis of implant were 0° (parallel to implantlongitudinal axis), 0°, 0°. Two 5 cm length segments of plate were putinto a tube mold such that parallel fiber orientation was also parallelto the longitudinal of the pin. The plate segments were thus molded intotube form to form tubes where orientation of layers relative tolongitudinal axis of implant were 0° (parallel to implant longitudinalaxis), 0°, 0°.

For amorphous alignment samples (n=3), plates of 0.5-0.6 mm wereproduced by compression molding three 0.18 mm thick layers ofbiocomposite material. Plates were each comprised of the PLDLA polymerwith embedded continuous fibers that were not uni-directionally alignedbut rather the layers were chopped into segments of approximately 3 mmand then molded together into the rectangular plates in bulk. Two 5 cmlength segments of plate were put into a tube mold. The plate segmentswere thus molded into tube form to form tubes with amorphous alignment.

Implant pins samples were tested for Flexural strength, Elastic modulusand Maximum load according to modified ASTM D790-10 with a 500N loadcell and a 3 point bending fixture (220Q1125-95, TestResources, MN,USA). Load span was 25.4 mm and cross head speed was set at 2 mm/min.

Flexural modulus was calculated according to:

$\begin{matrix}{\sigma_{\max} = \frac{8\; F_{\max}{Ld}_{0}}{\pi\left( {d_{0}^{4} - d_{i}^{4}} \right)}} & (1)\end{matrix}$

Where d0 is the outer diameter of the tube, di is the inner diameter ofthe tube and L is the support span.

Flexural Elastic modulus was calculated according to:

$\begin{matrix}{E = \frac{4\mspace{11mu}{mL}^{3}}{3{\pi\left( {d_{0}^{4} - d_{i}^{4}} \right)}}} & (2)\end{matrix}$Results

Table 5 shows the numerical summary of the various mechanical parametersfor the pins for material aligned in parallel, tested and thencalculated as described above. Table 6 shows the corresponding resultsfor amorphous (non-aligned) pins. With the exception of volume anddensity, pins made from the parallel aligned material had nearly fourtimes as great mechanical properties as pins made from the amorphousmaterial.

TABLE 5 Mean values and standard deviations of mechanical properties forparallel aligned pins as compared with amorphous (non-aligned) pinsFlexural Strength Density Sample E [MPa] [MPa] [gr/ml] Max Load [N]Volume [mm³] Parallel Tubes 8890.74 ± 1209.5 158.62 ± 19.3 1.47 ± 0.0219.82 ± 3.2  121.88 ± 7.06 (n = 7) Amorphous Tubes 2907.13 ± 730.9 40.15 ± 7.8 1.35 ± 0.04 4.82 ± 0.68 138.52 ± 2.96 (n = 3) Parallel to306% 395% Amorphous Anisotropocity (%)

FIG. 8 is a photograph of a representative hollow pin implant, 5 cmlength, 2 mm OD, 1 mm ID. FIG. 8A is a photo of the pin along itslength; FIG. 8B is a photo of the cross-section of the pin.

Example #6

Below example describes production of reinforced biocomposite pinimplants that are not hollow.

Materials and Methods

Pin implants of dimensions appropriate for small bone fixation (2 mm OD,5 cm) were made of composite material of composition as described inExample 1. Pin implants were manufactured in two steps. Plates of0.5-0.6 mm were produced by compression molding three 0.18 mm thicklayers of biocomposite material. Plates were each comprised of the PLDLApolymer with embedded uni-directionally aligned continuous fibers whereorientation of layers relative to longitudinal axis of implant were 0°(parallel to implant longitudinal axis), 0°, 0°. Four 5 cm lengthsegments of plate were put into a cylinder mold such that parallel fiberorientation was also parallel to the longitudinal of the pin. The platesegments were thus molded into cylinder form to form cylinders whereorientation of layers relative to longitudinal axis of implant were 0°(parallel to implant longitudinal axis), 0°, 0°.

Implant pins were tested for Flexural strength, Elastic modulus andMaximum load according to modified ASTM D790-10 with a 500N load celland a 3 point bending fixture (220Q1125-95, TestResources, MN, USA).Load span was 25.4 mm and cross head speed was set at 2 mm/min.

Flexural modulus was calculated according to:

$\begin{matrix}{\sigma_{\max} = \frac{8\; F_{\max}L}{{\pi d}_{0}^{3}}} & (1)\end{matrix}$

Where d₀ is the outer diameter of the cylinder and L is the supportspan.

Flexural Elastic modulus was calculated according to:

$\begin{matrix}{E = \frac{4\mspace{11mu}{mL}^{3}}{3{\pi d}_{0}^{4}}} & (2)\end{matrix}$Results

TABLE 7 Mean values and standard deviations of mechanical properties (n= 3). Flexural Strength Density Max Load Volume E [MPa] [MPa] [gr/ml][N] [mm³] Full 9536.53 ± 1348.7 202.82 ± 90.7 1.403 ± 0.003 24.79 ±10.12 169.58 ± 6.6 Cylinders

FIG. 9 is a photograph of a representative pin, 5 cm length, 2 mm OD.FIG. 9A is a photo of the pin along its length; FIG. 9B is a photo ofthe cross-section of the pin.

Example #7

The below example describes how anisotropic biocomposite implants retaina high amount of mechanical properties (modulus and strength) afterexposure to degradation conditions.

Materials and Methods

Rectangular testing samples (dimensions 50.8 mm×12.7 mm×0.75 mm),simulating plates used for small bone fixation, were produced usingreinforced composite material. Material composite was as described inExample 1.

Samples were produced by compression molding of five layers of compositematerial. Each layer was 0.18 mm thick. Five layer samples were eachcomprised of the PLDLA polymer with embedded uni-directionally alignedcontinuous fibers where orientation of layers relative to longitudinalaxis of implant were 0° (parallel to implant longitudinal axis), 45°,0°, −45°, 0°.

Implant samples were tested for Flexural strength, Elastic modulus andMaximum load according to ASTM D790-10 with a 500N load cell and a 3point bending fixture (220Q1125-95, TestResources, MN, USA). Load spanwas 25.4 mm and cross head speed was set at 1.536 mm/min. Implants weretested either at time=0 or after incubation in simulated body fluid(SBF). SBF was comprised of: 142 Na+, 5 K+, 1.5 Mg 2+, 2.5 Ca2+, 147.8Cl−, 4.2 HCO3−, 1 HPO43−, 0.5 SO4 2− mol/m3. Samples were incubated inSBF at 37 degrees C. in a shaking incubator (Wis-30 shaking incubator,Witeg, Germany) at 30 rpm for five days.

Results

Flexural Strength Max Load Density Volume E [MPa] [MPa] [N] [gr/ml][mm³] T₀ 10859.44 ± 163.6  281.59 ± 2.97  43.37 ± 0.91 1.47 ± 0.002479.33 ± 12.29 5 days, 37 C. 9694.59 ± 1322.5 188.24 ± 39.85 37.84 ±1.69 1.47 ± 0.03  550.05 ± 85.07

Table 8 shows the mean values and standard deviations of mechanicalproperties of the implants at t0 (n=2) and after 5 days at 37 C (n=3),demonstrating degradation after this elapsed time.

FIG. 10 shows the decrease in mechanical properties due to incubationunder conditions that force degradation. These results show that after 5days of simulated strength degradation, implants retained >60% offlexural strength, >85% of Modulus and Max load.

Additionally, implant swelling was measured following the incubation at37 C for 5 days, with thickness of implants increasing by 1.9% andoverall volume by 2.8%.

Example #8

The below example describes how anisotropic biocomposite implants retaina high amount of mechanical properties (modulus and strength) afterexposure to degradation conditions.

Materials and Methods

Rectangular testing samples (dimensions 50.8 mm×12.7 mm×0.75 mm),simulating plates used for small bone fixation, were produced usingreinforced composite material. Material composite was as described inExample 1.

Samples were produced by compression molding of five layers of compositematerial. Each layer was 0.18 mm thick. Five layer samples were eachcomprised of the PLDLA polymer with embedded uni-directionally alignedcontinuous fibers where orientation of layers relative to longitudinalaxis of implant were 0° (parallel to implant longitudinal axis), 45°,0°, −45°, 0°.

Implant samples were tested for Flexural strength, Elastic modulus andMaximum load according to ASTM D790-10 with a 500N load cell and a 3point bending fixture (220Q1125-95, TestResources, MN, USA). Load spanwas 25.4 mm and cross head speed was set at 1.536 mm/min. Implants weretested either at time=0 or after incubation in simulated body fluid(SBF). SBF was comprised of: 142 Na+, 5 K+, 1.5 Mg 2+, 2.5 Ca2+, 147.8Cl−, 4.2 HCO3−, 1 HPO43−, 0.5 SO4 2− mol/m3. Samples were incubated inSBF at 37 degrees C. in a shaking incubator (Wis-30 shaking incubator,Witeg, Germany) at 30 rpm for one day.

Results

Flexural Strength Density Volume E [MPa] [MPa] Max Load [N] [gr/ml][mm³] T0 11416.92 ± 403.7 289.67 ± 20.9 88.45 ± 7.5  1.45 ± 0.05 668.49± 23.5 24 hrs, 37 C.  11698.2 ± 502.5 260.05 ± 14.2 74.04 ± 5.25 1.50 ±0.03 638.58 ± 55.2

Table 9 shows the mean values and standard deviations of mechanicalproperties of The implants before and after incubation at 37 C in SBFfor 24 hrs (n=4).

After 24 hour incubation, there was no change in elastic modulus, >85%of flexural strength was retained, and >20% of max load.

Example #9

Below example describes production of hollow pin implants withreinforced biocomposite materials. As with plates, hollow pins withalignment with anisotropic characteristics, result in higher mechanicalproperties in the desired bending force parameters.

Materials and Methods

Hollow pin implants of dimensions appropriate for small bone fixation (2mm OD, 1 mm ID, 5 cm length) were made of composite material ofcomposition as described in Example 1. Pin implants were manufactured intwo steps and two types of pin implants were produced: hollowcylindrical pins and full cylindrical pins.

For hollow pins (n=3), plates of 0.5-0.6 mm were produced by compressionmolding three 0.18 mm thick layers of biocomposite material. Plates wereeach comprised of the PLDLA polymer with embedded uni-directionallyaligned continuous fibers where orientation of layers relative tolongitudinal axis of implant were 0° (parallel to implant longitudinalaxis), 0°, 0°. One 5 cm length segment of plate was put into each sideof a tube mold (total of two segments) such that parallel fiberorientation was also parallel to the longitudinal of the pin. The platesegments were thus molded into tube form to form tubes where orientationof layers relative to longitudinal axis of implant were 0° (parallel toimplant longitudinal axis), 0°, 0°.

For full cylindrical pins (n=3), plates of 0.5-0.6 mm were produced bycompression molding three 0.18 mm thick layers of biocomposite material.Plates were each comprised of the PLDLA polymer with embeddeduni-directionally aligned continuous fibers where orientation of layersrelative to longitudinal axis of implant were 0° (parallel to implantlongitudinal axis), 0°, 0°. Four 5 cm length segments of plate were putinto a cylindrical mold such that parallel fiber orientation was alsoparallel to the longitudinal of the pin. The plate segments were thusmolded into cylinder form to form cylinders where orientation of layersrelative to longitudinal axis of implant were 0° (parallel to implantlongitudinal axis), 0°, 0°.

Implant samples were tested for tensile strength, tensile modulus andmaximum load according to modified ASTM D3039M with a 5 KN load cell andan appropriate fixture (220Q1125-95, TestResources, MN, USA). Samplespan was 30 mm at the beginning of the test and cross head speed was setat 2 mm/min. Dimensions, weight and density of samples were recorded.

Results

Perhaps unsurprisingly, measures of mechanical strength (includingelastic module, tensile strength and max load) were all significantlyhigher for full (non-hollow) pins as compared to hollow pins, as shownin Tables 10 and 11.

TABLE 10 Mean values and standard deviations of mechanical properties ofhollow pin implants (n = 3) and full pin implants (n = 3). UltimateTensile tensile strength strain Density Volume E [MPa] [MPa] [mm/mm] MaxLoad [N] [gr/ml] [mm3] Hollow Pin 8244.3 ± 1379.8 78.01 ± 32.6  0.026 ±0.008 261.85 ± 113.3 1.41 ± 0.06 2.548 ± 0.17 Tensile Full Pin 10724.7 ±969.7  132.9 ± 23.09 0.029 ± 0.002 431.77 ± 75.9  1.43 ± 0.03  3.25 ±0.18 Tensile

Notably, the ratio of modulus as tested in tensile testing betweenhollow pins and full pins was 0.77 and the ratio of tensile strength was0.59. For similar pins, as described in examples 5 and 6, the ratio ofmodulus as tested in flexural testing between hollow pins and full pinswas 0.93 and the ratio of flexural strength was 0.78. These resultssuggest that the same 25% loss in volume between a full and hollowcylindrical geometry results in a different effect on modulus andstrength depending on the axis of mechanical testing (tensile orflexural). More strength and modulus are retained for bending resistance(flexural axis) than are retained for elongation resistance (tensileaxis) in the hollow geometry.

Example #10

Composite material technology can result in performance unattainable byindividual constituents, achieving diverse performance demands thatcould not be met by one material. A unique combination of strength,stiffness, density and degradation rate is achieved based on thestructural composition and orientation of fibers inside the implants.

A mechanical simulations of fiber orientations and structuralcompositions using the above-described aligned reinforced biocompositematerial was performed. The simulation suggested fiber orientations andstructural compositions that best fit the bending force load conditionsinvolved in many applications of orthopedic bone fixation. Biomechanicaldesign of implant per clinical application allows for maximizingclinical benefit by reducing implant size and the amount of foreignmaterial being implanted, achieving both required strengths and desiredrate of implant absorption.

FIG. 11 shows a graphical finite elements simulation. FIG. 11A showsforce distribution on a hollow cylinder pin implant with a wallthickness made of 5 layers as demonstrated in FIG. 11B.

Finite element modeling on a hollow bone fixation pin was performed toevaluate possible layer set ups that can support the expectedbiomechanical load (FIG. 1). Exact fiber orientation per layer greatlyaffects the performance of an implant. Table 12 shows how an increase in10 [N] for the buckling load of an implant in a single direction can betheoretically achieved using different layer structures.

TABLE 12 Finite element simulation results on a 2 mm pin implant fordifferent layer configurations. Orientation presented as: inner (left)to outer (right). Simulation confirms that higher buckling loads can bereached when optimizing layer orientation. In this example optimizingcan result in an increase in buckling load from 23 [N] to 32 [N]Configuration Bending stiffness [N/mm] Buckling load [N] 0/0/0/45/−450.554 22.7 45/0/0/0/−45 0.589 24.0 0/45/0/−45/0 0.591 24.2 45/−45/0/0/00.626 25.7 20/−20/20/−20/20 0.610 24.8 15/−15/15/−15/15 0.629 29.110/−10/10/−10/10 0.788 32.5

It will be appreciated that various features of the invention which are,for clarity, described in the contexts of separate embodiments may alsobe provided in combination in a single embodiment. Conversely, variousfeatures of the invention which are, for brevity, described in thecontext of a single embodiment may also be provided separately or in anysuitable sub-combination. It will also be appreciated by persons skilledin the art that the present invention is not limited by what has beenparticularly shown and described hereinabove.

All references cited or described herein are hereby incorporated byreference as if set forth herein to the extent necessary to support thedescription of the present invention and/or of the appended claims.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to additionally embrace all suchalternatives, modifications and variations that fall within the spiritand broad scope of the appended claims.

What is claimed is:
 1. An orthopedic fixation implant comprisingabsorbable structural material, wherein strength and stiffnessproperties are anisotropic; the absorbable structural materialcomprising a reinforcement filler, wherein said absorbable structuralmaterial further comprises a biodegradable polymer; wherein an averagedensity of the absorbable structural material is in a range of 1.3-3.0g/cm³; wherein said reinforcing filler comprises a plurality ofreinforcing fibers and wherein a weight ratio of reinforcing fibers tosaid biodegradable polymer is in the range of 1:1 to 1:3; and wherein apercentage of reinforcing fibers is in the range of 40% to 50% weightper weight; wherein a plurality of said reinforcement fibers arearranged in parallel to a longitudinal axis of the implant.
 2. Theimplant of claim 1, wherein the biodegradable composite has a maximumflexural modulus in the range of 6 GPa to 30 GPa and flexural strengthin the range of 100 MPa to 1000 MPa.
 3. The implant of claim 1, havingimproved mechanical properties in at least one mechanical axis orparameter as compared with at least one other mechanical axis orparameter within the same implant, such that the implant is anisotropic;wherein said mechanical parameter comprises one or more of bendingstrength and stiffness (resistance to bending force), tensile strengthand stiffness (resistance to tensile force), compression strength andstiffness (resistance to compression force), shearing strength andstiffness (resistance to shearing force), or torsional strength andstiffness (resistance to torsional force); where in properties areanisotropic of at least 10%, at least 20%, at least 30%, 40%, 50%, 60%,70%, 80%, 90% or 100%, or any number in between.
 4. The implant of claim1, wherein said biodegradable polymer comprises a homopolymer or acopolymer; wherein said copolymer comprises a random copolymer, blockcopolymer, or graft copolymer; and wherein said biodegradable polymercomprises a linear polymer, a branched polymer, or a dendrimer, ofnatural or synthetic origin; wherein said biodegradable polymercomprises lactide, glycolide, caprolactone, valerolactone, carbonates(e.g., trimethylene carbonate, tetramethylene carbonate), dioxanones(e.g., 1,4-dioxanone), δ-valerolactone, 1, dioxepanones (e.g.,1,4-dioxepan-2-one and 1,5-dioxepan-2-one), ethylene glycol, ethyleneoxide, esteramides, y-hydroxyvalerate, β-hydroxypropionate,alpha-hydroxy acid, hydroxybutyrates, poly (ortho esters), hydroxyalkanoates, tyrosine carbonates, polyimide carbonates, polyiminocarbonates, such as poly (bisphenol A-iminocarbonate) and poly(hydroquinone-iminocarbonate), polyurethanes, polyanhydrides, polymerdrugs (e.g., polydiflunisol, poly aspirin, and protein therapeutics),sugars; starch, cellulose and cellulose derivatives, polysaccharides,collagen, chitosan, fibrin, hyaluronic acid, polypeptides, proteins,poly (amino acids), polylactides (PLA), poly-L-lactide (PLLA),poly-DL-lactide (PDLLA); polyglycolide (PGA); copolymers of glycolide,glycolide/trimethylene carbonate copolymers (PGA/TMC); other copolymersof PLA, such as lactide/tetramethylglycolide copolymers,lactide/trimethylene carbonate copolymers, lactide/d-valerolactonecopolymers, lactide/ε-caprolactone copolymers, L-lactide/DL-lactidecopolymers, glycolide/L-lactide copolymers (PGA/PLLA),polylactide-co-glycolide; terpolymers of PLA, such aslactide/glycolide/trimethylene carbonate terpolymers,lactide/glycolide/ε-caprolactone terpolymers, PLA/polyethylene oxidecopolymers; polydepsipeptides; unsymmetrically- 3,6-substitutedpoly-1,4-dioxane-2,5-diones; polyhydroxyalkanoates, such aspolyhydroxybutyrates) PHB); PHB/b-hydroxyvalerate copolymers (PHB/PHV);poly-b-hydroxypropionate (PHPA); poly-p-dioxanone (PDS);poly-d-valerolactone-poly-ε-capralactone,poly(ε-caprolactone-DL-lactide) copolymers; methylmethacrylate-N-vinylpyrrolidone copolymers; polyesteramides; polyesters of oxalic acid;polydihydropyrans; polyalkyl-2-cyanoacrylates; polyurethanes (PU);polyvinylalcohol (PVA); polypeptides; poly-b-malic acid (PMLA):poly-b-alkanoic acids; polycarbonates; polyorthoesters; polyphosphates;poly(ester anhydrides); and derivatives, copolymers and mixturesthereof.
 5. The implant of claim 1, wherein the polymer is in a form ofa polymer matrix; wherein said polymer matrix comprises a polymerselected from the group consisting of PLLA (poly-L-lactide), PDLLA(poly-DL-lactide), PLDLA, PGA (poly-glycolic acid), PLGA(poly-lactide-glycolic acid), PCL (polycaprolactone), PLLA-PCL and acombination thereof.
 6. The implant of claim 5, wherein an inherentviscosity (IV) of the polymer matrix alone is in the range of 0.2-6dl/g, 1.0 to 3.0 dl/g, 1.5 to 2.4 dl/g, or 1.6 to 2.0 dl/g, wherein IVis measured according to a flow time of a polymer solution through anarrow capillary relative to the flow time of a pure solvent through thecapillary.
 7. The implant of claim 1, wherein if PLLA is used, thematrix comprises at least 30% 50%, or at least 70% PLLA; or wherein ifPDLA is used, the matrix comprises at least 5%, at least 10%, or atleast 20% PDLA.
 8. The implant of claim 1, wherein said weight ratio isin a range of 0.75:1 to 1.25:1.
 9. The implant of claim 8, wherein saidfibers comprise one or more of a biodegradable glass or glass-likematerials, a ceramic, a mineral composition (optionally including one ormore of hydroxyapatite, tricalcium phosphate, calcium sulfate, calciumphosphate), a cellulosic material, a nano-diamond, or any other fillerknown in the art to increase the mechanical properties of abioabsorbable polymer, or wherein said fiber comprises a bioabsorbableglass, ceramic, or mineral composition.
 10. The implant of claim 9,wherein said biodegradable glass has oxide compositions in the followingmol. % ranges (as a percent over the glass fiber composition): Na₂O:11.0-19.0 mol. %, CaO: 9.0-14.0 mol. %, MgO: 1.5-8.0 mol. %, B₂O₃:0.5-3.0 mol. %, Al₂O₃: 0-0.8 mol. %, P₂O₃: 0.1-0.8 mol. %, SiO₂: 67-73mol. %.
 11. The implant of claim 10 where said ranges are the followingmol. % ranges: Na₂O: 12.0-13.0 mol. %, CaO: 9.0-10.0 mol. %, MgO:7.0-8.0 mol. %, B₂O₃: 1.4-2.0 mol. %, P₂O₃: 0.5-0.8 mol. %, SiO₂: 68-70mol. %.
 12. The implant of claim 1, wherein an average fiber diameter isbetween 5 and 50 um.
 13. The implant of claim 12, wherein a tensilestrength of the reinforcement fiber is in the range of 1200-2800 MPa, orwherein an elastic modulus of the reinforcement fiber is in the range of30-100 GPa, or a combination thereof.
 14. The implant of claim 1 whereinat least 50% of elastic modulus is retained following exposure tosimulated body fluid (SBF) at 50 C for 3 days, or at least 70% isretained, and even at least 80% is retained.
 15. The implant of claim 1wherein implant is an orthopedic implant and is selected from the groupsincluding bone fixation plates, intramedullary nails, joint (hip, knee,elbow) implants, spine implants, screws, pins, wires, soft tissueanchors and other devices for such applications such as for fracturefixation, tendon reattachment, spinal fixation, and spinal cages. 16.The implant of claim 1 wherein a reinforcing fiber diameter is in arange of 2-40 um, 8-20 um, or 12-18 um (microns).
 17. The implant ofclaim 1, wherein the orthopedic fixation implant is a pin, plate, screw,nail, fiber, sheet, rod, staple, clip, needle, tube, anchor, cable, tie,or wire tie.
 18. The implant of claim 17, wherein the implant is a pin,screw, plate, nail, rod, staple, or wire.